Effect of erythropoietin on cognitive side-effects of electroconvulsive therapy in depression: A randomized, double-blind, placebo-controlled trial.

Electroconvulsive therapy (ECT) is one of the most effective and rapid-acting treatment for severe depression but is associated with cognitive side-effects. Identification of add-on treatments that counteract these side-effects would be very helpful. This randomized, double-blinded, placebo-controlled, parallel-group study investigated the effects of four add-on erythropoietin (EPO; 40,000 IU/ml) or saline (placebo) infusions over 2.5 weeks of ECT (eight ECT sessions) in severely depressed patients with unipolar or bipolar depression. Neuropsychological assessments were conducted pre-ECT, three days after the eighth ECT (week 4), and at a 3-month follow-up. Further, functional magnetic resonance imaging (fMRI) was conducted after the eighth ECT. The primary outcome was change from pre- to post-ECT in a 'speed of complex cognitive processing' composite. Secondary outcomes were verbal and autobiographical memory. Of sixty randomized patients, one dropped out before baseline. Data were thus analysed for 59 patients (EPO, n = 33; saline, n = 26), of whom 28 had fMRI data. No ECT-related decline occurred in the primary global cognition measure (ps≥0.1), and no effect of EPO versus saline was observed on this outcome (ps≥0.3). However post-ECT, EPO-treated patients exhibited faster autobiographical memory recall than saline-treated patients (p = 0.02), which was accompanied by lower memory-related parietal cortex activity. The absence of global cognition changes with ECT and EPO, coupled with the specific impact of EPO on autobiographical memory recall speed and memory-related parietal cortex activity, suggests that assessing autobiographical memory may provide increased sensitivity in evaluating and potentially preventing cognitive side-effects of ECT. TRIAL REGISTRATIONS: ClinicalTrials.gov: NCT03339596, EudraCT no.: 2016-002326-36.

Cognitive Adverse Effects of Electroconvulsive Therapy: A Discrepancy Between Subjective and Objective Measures?

OBJECTIVES: The character and duration of cognitive adverse effects of electroconvulsive therapy (ECT) are unclear. This study investigated (1) the sensitivity of a short cognitive test battery to cognitive adverse effects of ECT, (2) the relation between subjective and objective cognitive adverse effects, and (3) patient characteristics associated with more subjective than objective adverse effects. METHODS: Forty-one patients with unipolar or bipolar depression referred to ECT underwent assessments at baseline, 5 to 7 days post-ECT, and 3 months post-ECT. Patients rated their fear of various aspects of ECT on a visual analog scale. At each assessment, patients were evaluated for depressive symptoms, completed the Screen for Cognitive Impairment in Psychiatry (SCIP) and Trail Making Test-Part B (TMT-B), and rated their cognitive difficulties. RESULTS: Patients feared cognitive adverse effects and lack of treatment efficacy more than other aspects of ECT. The SCIP and TMT-B revealed transient decline in objective cognition after ECT, which was reversed after 3 months. Patients presented with more subjective than objective cognitive difficulties at baseline and more subjective than objective cognitive adverse effects of ECT. This discrepancy was significantly reduced at follow-up. Younger age and poorer objective cognition pretreatment were associated with more subjective than objective cognitive adverse effects 5 to 7 days after ECT. CONCLUSIONS: The SCIP and TMT-B are sensitive to cognitive adverse effects of ECT. Patients show more subjective than objective cognitive adverse effects of ECT. These insights can be used clinically to inform patients of treatment choice and expected cognitive consequences.